SummaryLevels of eight complement components and two control proteins, were determined on cord serum from normal full term neonates and serum from healthy infants aged 1 and 6 months. For all proteins, the levels were below the adult normal at birth and rose toward the adult range by age 6 months. In a second group of 271 patients, ages 1-36 months, serum Clq and properdin levels were measured. For both proteins, the mean values in early infancy were more than two SD below the adult range and did not reach the adult range until 18-21 months of age. The Clq concentration was more variable than that for any other component studied. In infants from 11 months-3 yr of age, Clq levels correlated with serum IgG levels, but properdin levels did not.
The serums of patients with hypocomplementemic glomerulonephritis contain a substance that combines with a normal serum cofactor in the presence of magnesium ion to specifically cleave the third component of complement. This lysis of C'3 is 80 to 90 percent complete in 20 minutes at 37 degrees C and pH 7. Neither the nephritic factor nor its cofactor is identifiable with the complement system.
Two biologically and chemically distinct anaphylatoxins (ATs) could be generated in whole human serum after removal of the AT inactivator (AI) by immune-absorption or after inhibition of AI with 1 M epsilon-aminocaproic acid (EACA). Both human ATs could be generated by treatment of serum with antigen-antibody complexes, which activate the classical complement pathway, and with inulin or yeast, both of which trigger the alternate pathway. The ATs were isolated from serum in active form and characterized as C3a and C5a. Although human C3a had been characterized previously, C5a had not. The molecular weight of human C5a AT was 17,500; its electrophoretic mobility at pH 8.5 was –1.7 x 10–5 cm2 V–1 s–1. The minimal effective concentration in vitro was 7.5 x 10–10 M. The minimal effective doses of human C5a in producing a wheal and erythema in the human skin was 1 x 10–15 mol. The results strongly suggest a biological function for both ATs and indicate that the expression of their activity is controlled by the AI of normal blood plasma.
All immune origin of glomerulonephritis, with complement playing a major role, was first suspected 50 yr ago when it was found that serum complement levels in nephritis were often low. Only recently however, with the identification of individual components, have details of the complement reaction become susceptible to investigation. It is already apparent that there are differences in the way in which complement is involved in nephritis. For example, serum levels of individual components have been shown to be variably reduced depending upon the type of nephritis (1-3). Furthermore, deposition of C3 in the glomeruli occurs in many cases in which C3 and total complement levels have remained normal during the course of the disease (4-6). In other types of nephritis, however, the configuration of C3 deposition correlates well with the supposed target of the immune reaction (4, 5).The participation of complement in producing the type of nephritis designated hypocomplementemic persistent or membranoproliferative is of special interest. In this disease CHs0 and C3 may remain at very low levels over long periods (6, 7) and C3 is usually found in the glomerular capillary walls by immunofluorescent techniques, often without the presence of identifiable IgG. 1 The persistently reduced serum levels of C3 have been explained by some as the result of diminished synthesis of C3 (8) and ascribed by others to an ongoing complement reaction in the glomeruli in which C3 is continuously being broken down (9). Recent observations suggest that a site of complement breakdown may be circulating plasma. Inactivators of guinea pig (10) and human (11) complement have been found in the serum of patients with acute, chronic hypocomplementemic, and lupus nephritis, and in a previous communication from this ]nboratory, Spitzer et al. (12) reported the presence of a factor in the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.